1. Field of the Invention
Steroids play an important role in life processes being the basic structure for the male and female hormones, corticosteroids and bile acids, as well as the basis for many synthetic reagents, such as synthetic male and female hormones, anti-inflammatory agents, and the like. The naturally occurring steroids which the synthetic steroids normally mimic have a complex polycyclic structure with particular geometry as to the ring fusions, as well as substituents on the ring, and also have a specific stereoisomerism. Any synthesis must therefore recognize the need to provide a product having the required geometry and stereochemistry.
For the most part the industry has relied on the use of naturally occurring plant steroids which were then modified to provide the necessary substituents. Many of the procedures were fairly extensive since the plant steroids did not provide readily available functionalities at desired sites, such as C-11, nor at sites adjacent to C-11 which would allow for introduction of a particular functionality. In addition, the plant steroids were only difficultly modifiable, where hydrocarbon groups, such as angular methyl groups were modified, either by introducing a polar functionality, or by changing the alkyl group.
In developing a complete synthesis from small molecules to a steroid structure there are a number of considerations. Desirably, resolution which allows for subsequent asymmetric induction should be afforded relatively early in the synthesis. Reactions in the course of the synthesis should not adversely affect earlier geometry. Formation of functionalities should afford the desired spatial configuration upon cyclization. Therefore, a synthetic scheme must be considered as a single entity, in that earlier synthetic steps must anticipate subsequent synthetic steps, and subsequent synthetic steps must take into account their effect on functionalities which have been previously introduced.
2. Description of the Prior Art
Cyclization of monocyclic polyunsaturated compounds has been reported in a number of articles as well as patents. U.S. Pat. Nos. 3,558,672 and 3,598,845 report cyclization of different precursors to the perhydrocyclopentanophenanthrene structure. Scientific articles of interest include Johnson, et al., J. Am. Chem. Soc., 90, 2991 (1968); ibid, 92, 741 (1970); and ibid, 93, 4432 (1971).